The enantioselective total synthesis of four members of the recently discovered pumiliotoxin-A class of alkaloids from L-proline is proposed. These structurally novel indolidizine alkaloids have been demonstrated to possess potent cardiotonic and myotonic activity, and are not readily available from natural sources. Specifically we propose to prepare by enantioselective total synthesis the chiral toxins 251D, allo-267A, pumiliotoxin-A, and pumiliotoxin-B. In particular we seek to develop efficient synthetic procedures such that the target compounds will be available, via total synthesis, in sufficient quantities for detailed pharmacological evaluations. We moreover propose a rational program of analog synthesis and testing which should yield basic structure-activity information, and perhaps yield compounds of greater activity than natural materials. Our proposed synthetic approach to toxin 251D is founded on preliminary studies which have demonstrated the utility of chiral epoxide synthons prepared from L-proline.